Dengue virus binding to human leukocyte cell lines: receptor usage differsbetween cell types and virus strains

Monocyte macrophages (M phi) are thought to be the principal target cells f or the dengue viruses (DV), the cause of dengue fever and hemorrhagic fever . Cell attachment is mediated by the virus envelope (E) protein, but the ho st-cell receptors remain elusive. Currently, candidate receptor molecules i nclude proteins, Fc receptors, glycosaminoglycans (GAGs) and lipopolysaccha ride binding CD14-associated molecules. Here, we show that in addition to M phi, cells of the T- and B-cell lineages, and including cells lacking GAGs , can bind and become infected with DV. The level of virus binding varied w idely between cell lines and, notably, between virus strains within a DV se rotype. The latter difference may be ascribable to one or more amino acid d ifferences in domain II of the E protein. Heparin had no significant effect on DV binding, while heparinase treatment of cells in all cases increased DV binding, further supporting the contention that GAGs are not required fo r DV binding and infection of human cells. In contrast to a recent report, we found that lipopolysaccharide (LPS) had either no effect or enhanced DV binding to, and infection of various human leukocyte cell lines, while in a ll virus-cell combinations, depletion of Ca2+/Mg2+ enhanced DV binding. Thi s argues against involvement of beta (2) integrins in virus-host cell inter actions, a conclusion in accord with the demonstration of three virus bindi ng membrane proteins of < 75 kDa. Collectively, the results of this study q uestion the purported exclusive importance of the E protein domain III in D V binding to host cells and point to a far more complex interaction between various target cells and, notably, individual DV strains. (C) 2001 Elsevie r Science B.V. All rights reserved.